Translocation of gold nanoparticles across the lung epithelial tissue barrier: Combining in vitro and in silico methods to substitute in vivo experiments

Bachler, Gerald; Losert, Sabrina; Umehara, Yuki; Goetz, Natalie von; Rodríguez‐Lorenzo, Laura; Petri‐Fink, Alke; Rothen‐Rutishauser, Barbara; Hungerbuehler, Konrad

doi:10.1186/s12989-015-0090-8

Cited by 86 publications

(81 citation statements)

References 75 publications

(135 reference statements)

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“…Translocation of Au NPs in sizes between 2 and 80 nm across human and murine alveolar cell monolayers was similar to in vivo data and ranged between 0.2 and 2 % of the applied particles (Bachler et al 2015). Translocation was inversely related to particle size and constant up to 100 ng/cm 2 .…”

Section: Respiratory Routesupporting

confidence: 51%

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Frőhlich

Roblegg

2016

Arch Toxicol

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Nanoparticles (NPs) present in environment, consumer and health products, food and medical applications lead to a high degree of human exposure and concerns about potential adverse effects on human health. For the general population, the exposure through contact with the skin, inhalation and oral uptake are most relevant. Since in vivo testing is only partly able to study the effects of human oral exposure, physiologically relevant in vitro systems are being developed. This review compared the three routes taking into account the estimated concentration, size of the exposed area, morphology of the involved barrier and translocation rate. The high amounts of NPs in food, the large absorption area and the relatively high translocation rate identified oral uptake as most important portal of entry for NPs into the body. Changes of NP properties in the physiological fluids, mechanisms to cross mucus and epithelial barrier, and important issues in the use of laboratory animals for oral exposure are mentioned. The ability of in vitro models to address the varying conditions along the oro-gastrointestinal tract is discussed, and requirements for physiologically relevant in vitro testing of orally ingested NPs are listed.

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Section: Respiratory Routesupporting

confidence: 51%

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Frőhlich

Roblegg

2016

Arch Toxicol

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“…This estimate is consistent with those derived from pulmonary instillation of particles in animal models, 33,34 and those derived from in vitro – in silico modeling. 35 The majority of inhaled nanoparticles are retained in the alveolar region and are slowly cleared over time. 25 In the present study, gold was still detectable in blood and urine at 3 months, consistent with ongoing translocation of gold either through the alveolar membrane or possibly via the gastrointestinal tract after clearance by the mucociliary escalator.…”

Section: Results and Discussionmentioning

confidence: 99%

Inhaled Nanoparticles Accumulate at Sites of Vascular Disease

Miller¹,

Raftis²,

Langrish³

et al. 2017

ACS Nano

487

287

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The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2–200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.

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“…Wagner et al observed that in vitro PEI/DNA particles that are formed by simple pipetting at low N/P ratios tend to aggregate and increase in overall size which, in turn, leads to more efficient gene knockdown of the aggregated particles in vitro due to differences in sedimentation rates [24]. However, in vivo sedimentation plays a secondary role, and larger particles are phagocytosed and cleared by macrophages more rapidly, while smaller particles more efficiently diffuse through mucus and surfactant in the lung and are more efficiently endocytosed by the epithelium [39]. Additionally, another possible explanation for the increase in gene efficiency lies in the possibilty for our particles to undergo transcytosis.…”

Section: Resultsmentioning

confidence: 99%

The impact of microfluidic mixing of triblock micelleplexes on in vitro $/$ in vivo gene silencing and intracellular trafficking

et al. 2017

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The triblock copolymer polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG) has been shown to spontaneously assemble into nano-sized particulate carriers capable of complexing with nucleic acids for gene delivery. The objective of this study was to investigate micelleplex characteristics, their in vitro and in vivo fate following microfluidic preparation of siRNA nanoparticles compared to the routinely used batch reactor mixing technique. Herein, PEI-PCL-PEG nanoparticles were prepared with batch reactor or microfluidic mixing techniques and characterized by various biochemical assays and in cell culture. Microfluidic nanoparticles showed a reduction of overall particle size as well as a more uniform size distribution when compared to batch reactor pipette mixing. Confocal microscopy, flow cytometry and qRT-PCR displayed the subcellular delivery of the microfluidic formulation and confirmed the ability to achieve mRNA knockdown. Intratracheal instillation of microfluidic formulation resulted in a significantly more efficient (p < 0.05) knockdown of GAPDH compared to treatment with the batch reactor formulation. The use of microfluidic mixing techniques yields an overall smaller and more uniform PEG-PCL-PEI nanoparticle that is able to more efficiently deliver siRNA in vivo. This preparation method may prove to be useful when a scaled up production of well-defined polyplexes is required.

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Translocation of gold nanoparticles across the lung epithelial tissue barrier: Combining in vitro and in silico methods to substitute in vivo experiments

Cited by 86 publications

References 75 publications

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Inhaled Nanoparticles Accumulate at Sites of Vascular Disease

The impact of microfluidic mixing of triblock micelleplexes on in vitro $/$ in vivo gene silencing and intracellular trafficking

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